POS0480 VITAMIN D AND ITS RECEPTOR (VDR) GENE EXPRESSION IN SKELETAL MUSCLE ASSOCIATE WITH DISEASE AND MUSCLE FUNCTION PARAMETERS IN IDIOPATHIC INFLAMMATORY MYOPATHIES
Authors: L. Vernerová, M. Vokurková, S. Oreska, M. Špiritović, M. Klein, T. Kropackova, V. Horvathova, M. Tomčík, J. Ukropec, B. Ukropcová, J. Vencovský
Journal: Annals of the Rheumatic Diseases (2022)

Background Idiopathic inflammatory myopathies (IIM) are chronic inflammatory disorders characterised, apart from extramuscular manifestations, by symmetrical progressive muscle weakness that may persist even after pharmacological suppression of inflammation, suggesting a significant involvement of nonimmune mechanisms. Low levels of vitamin D have been associated with several autoimmune diseases. Vitamin D is essential for the maintenance of skeletal muscle, and mounting evidence supports its relation to muscle damage, regeneration, and energy metabolism. Objectives The aim was to analyse vitamin D and the mediators of its function in muscle tissue of IIM patients, and to associate it with muscle health parameters. Methods A total of 46 IIM patients (40 females, 6 males; mean age 56.7±12.4; disease duration 6.5±6.0 years; dermatomyositis (21), polymyositis (18), necrotizing myopathy (7)) and 67 healthy controls (HC) (56 females, 11 males; mean age 50.9±14.7) were recruited. In total, 27 IIM patients participated in a 24-week intervention combining activities-of-daily-life, resistance and stability training [1]. Muscle biopsies from m. vastus lateralis (by Bergström needle) were obtained from 7 IIM patients before/after the 24-week training program, and from 13 control IIM patients, and 21 HC. Primary muscle cell cultures were established from these samples. Disease-associated parameters were evaluated by MYOACT/MITAX, MDI, VAS, HAQ, MMT8, FI-2 and CK, myoglobin, LD, ALT, AST, and CRP levels. Myostatin, as a myokine involved in muscle atrophy, was determined from serum samples by ELISA. Circulating concentrations of 25(OH) vitamin D (calcidiol) and active 1,25(OH) vitamin D (calcitriol) were measured by routine biochemistry techniques. Gene expression of vitamin D receptor (VDR) and 25-hydroxyvitamin D 1-alpha-hydroxylase (CYP27B1), an enzyme catalysing calcidiol conversion to hormonally active calcitriol, was determined by real-time PCR in muscle tissue and primary muscle cell cultures. Data are presented as mean ± standard deviation. Results Decreased levels of active 1,25(OH)D were observed in IIM patients compared to HC (125.0±45.4 vs. 164.7±49.2 pmol/l; p&lt;0.0001). No difference was found for 25(OH)D. The 24-week training program did not have an effect on 25(OH)D or 1,25(OH)D serum levels. 25(OH)D was significantly associated with CRP (r=-0.322, p=0.040), MITAX (r=-0.380, p=0.021) and HAQ (r=-0.370, p=0.017) in IIM patients, even after correction for BMI, gluccocorticoid (GC) and vitamin D daily supplementation dose. After 24 weeks of exercise, active 1,25(OH)D was positively associated with MMT8 (r=0.866, p&lt;0.0001), FI2 (r=0.608, p=0.013) and HAQ (r=-0.537, p=0.032) (corrected for BMI, GC and vit.D supplementation). Numerically higher gene expression of VDR and CYP27B1 was found in muscle tissue and primary muscle cells in IIM compared to HC. After the 24-week training, gene expression of both VDR and CYP27B1 in primary muscle cells decreased (p=0.031 and p=0.078, respectively). Associations of VDR gene expression with myoglobin (IIM: r=0.510, p=0.026; HC: r=0.473, p=0.035), MMT8 (IIM: r=-0.559, p=0.013), myostatin (IIM: r=-0.519, p=0.023; HC: r=0.586, p=0.005), and CK (HC: r=0.484, p=0.031) were observed in muscle tissue. CYP27B1 gene expression in the muscle was also associated with myoglobin (HC: r=0.501, p=0.024), MMT8 (IIM: r=-0.555, p=0.011) and VDR (IIM: r=0.561, p=0.012; HC: r=0.632, p=0.002). Conclusion Decrease of the biologically active form of vitamin D in circulation suggests an impairment of its metabolism in IIM. Vitamin D serum levels and gene expression of its receptor and activating enzyme in muscle tissue associate with disease activity and muscle function parameters indicating an important role of vitamin D in physical fitness and disease manifestations in IIM patients. References [1]Špiritović M, et al. Arthritis Res Ther. 2021;23(1):173. Acknowledgements This work was supported by the Ministry of Health of the Czech Republic grant nr. NU21-05-00322. Disclosure of Interests None declared.